This is a Phase I study designed to determine the MTD and assess the toxicity associated with clofarabine followed by fractionated cyclophosphamide in patients > 1 year of age or < 21 years of age with relapsed or refractory acute leukemias. There will be 25 to 35 patients enrolled. Cohorts of 3 to 6 patients each will receive escalated doses of clofarabine followed by fractionated cyclophosphamide until the MTD is reached. There will be no intra-patient dose escalation. Single-agent cyclophosphamide will be administered by 2-hour IVI on Day 0 of cycle 1. On Days 1, 2, and 3 and Days 8, 9, and 10 clofarabine will be administered by IVI 2 hours before each dose of cyclophosphamide (see the treatment schema below). A cycle is defined as 28 days.

To determine the feasibility, tolerability, toxicities, and MTD of clofarabine followed by fractionated cyclophosphamide in pediatric patients with relapsed or refractory acute leukemias. [ Time Frame: 1 cycle ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To obtain preliminary descriptive data of the biologic and pharmacodynamic effects of clofarabine followed by fractionated cyclophosphamide on marrow and circulating leukemic blasts in pediatric patients with relapsed or refractory acute leukemias. [ Time Frame: 1 cycle ] [ Designated as safety issue: Yes ]

Estimated Enrollment:

35

Study Start Date:

September 2007

Estimated Primary Completion Date:

January 2010 (Final data collection date for primary outcome measure)

Intervention Details:

Drug: Clofarabine

On Days 1, 2, and 3 and Days 8, 9, and 10 clofarabine will be administered by IVI 2 hours before each dose of cyclophosphamide

Drug: Cyclophosphamide

Single-agent cyclophosphamide will be administered by 2-hour IVI on Day 0 of cycle 1. On Days 1, 2, and 3 and Days 8, 9, and 10 clofarabine will be administered by IVI 2 hours before each dose of cyclophosphamide

Cardiac function must be normal per the institution normal as measured by echocardiogram (ECHO) within 7 days.

Patients should have no evidence of myositis as detected by abnormal serum creatine kinase and/or myoglobin.

Exclusion Criteria:

No chemotherapy, radiation, or major surgery within 2 weeks prior to first dose of study drug except for 5-azacytidine, thalidomide, hydroxyurea, imatinib (Gleevec), and interferon which must be discontinued at least 3 days before study entry and the patient should have recovered from the toxic side effects of such therapy. In the instance of progressive disease, anti-leukemia therapy may have been administered within the 2-week period as long but the subject should have recovered from the toxic effects of that therapy. Also, intrathecal therapy may be administered within the 2-week period for subjects with CNS disease.

Patients who have had an allogeneic or autologous hematopoietic stem cell transplant.

Patients must have discontinued all growth factors, except Procrit (epoetin), at least 1 week before study.

Patients with known HIV positive status or AIDS.

Patients with known active Hepatitis B, Hepatitis C or cirrhosis.

History of severe coronary artery disease, including myocardial infarction within the previous 3 months, arrhythmias other than atrial flutter or fibrillation requiring medication, or uncontrolled congestive heart failure.

Patients with active uncontrolled infection, fever of infection, or evidence for progressive disease by CT scans of the lungs, sinuses, or abdomen. Patients who are on antimicrobial therapy and stable, CT scans must have been stable for 4 weeks, may be enrolled but there must be no evidence of an active infection. Patients with fever due to leukemia may be enrolled.

Pregnant or lactating patients. Female patients of childbearing potential must have a negative serum pregnancy test within 14 days before study entry.

Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00852709

Locations

United States, Arizona

Phoenix Children's Hospital

Phoenix, Arizona, United States, 85016-7710

United States, Colorado

University of Colorado Health Sciences Center and The Children's Hospital

Aurora, Colorado, United States, 80045

United States, Florida

Pediatrix Hematology/Oncology University of Florida College of Medicine